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Anti-Ceramide Single-chain Variable Fragment Mitigates Radiation GI Syndrome Mortality Independent of DNA Repair

JCI Insight. 2021-03; 
Jimmy A Rotolo, Chii Shyang Fong, Sahra Bodo, Prashanth K B Nagesh, John D Fuller, Thivashnee Sharma, Alessandra Piersigilli, Zhigang Zhang, Zvi Fuks, Vijay K Singh, Richard Kolesnick
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PCR Cloning and Subcloning … antibody fragments of VH, VL, CH and CL were amplified according to the standard operating procedure for RACE at GenScript (GenScript, Piscataway, NJ). Amplified antibody fragments were separately cloned into a standard cloning vector using standard molecular cloning … Get A Quote

摘要

After 9/11, threat of nuclear attack on American urban centers prompted government agencies to develop medical radiation countermeasures to mitigate hematopoietic-acute radiation syndrome (H-ARS) and higher-dose gastrointestinal-ARS (GI-ARS) lethality. While re-purposing leukemia drugs that enhance bone marrow repopulation successfully treats H-ARS in pre-clinical models, no mitigator potentially deliverable under mass casualty conditions preserves GI tract. Here we generate anti-ceramide 6B5 single-chain variable fragment (scFv) and show subcutaneous 6B5 scFv delivery at 24h after a 90% lethal GI-ARS dose of 15Gy mitigates mouse lethality, despite administration after DNA repair is complete. We define an alter... More

关键词

Apoptosis, DNA repair, Endothelial cells, Stem cells, Vascular Biology